The field of lipid nutrition, including the public awareness of dietary modifications, has undergone a great number of changes in the last few years. Many people have replaced complex, saturated animal fats in their diets by polyunsaturated vegetable fats for health reasons, particularly in an attempt to control serum cholesterol levels. Most recently, fish oils have been suggested as a dietary supplement for cholesterol and triglyceride control and antithrombotic benefits. In addition, medium chain triglycerides ("MCT"), eight (C.sub.8)and ten (C.sub.10) carbon fatty acids bound to a glycerol backbone, have been used on an experimental basis, primarily in hospitals, as a nutrition source because of their rapid uptake and utilization by the body. Additional experimental work has been conducted with structured lipids, e.g., U.S. Pat. No. 4,528,197. However, none of these nutritional programs have been a panacea; there have been numerous problems with absorption of the fatty acids into the body and/or health problems in patients. These problems occur, in part, because of the type of fatty acid mixture chosen. Accordingly, there still remains a need for a better lipid nutrition supplement.
An understanding and/or modification of the lipids themselves and their delivery system is necessary for designing a better nutritional program. Lipids are primarily long chain polyunsaturated fatty acids which can be classified into three major groups: .omega.3, .omega.6 and .omega.9. The classes are based on the location of the double bond closest to the methyl end of the fatty acid; that is, if the closest double bond is between the third and fourth carbon atoms from the methyl group, the molecules are .omega.3 fatty acids while if the double bond is between the sixth and seventh carbon atoms, the molecules are classified as .omega.6 fatty acids. Man and other mammals can desaturate or elongate the fatty acid chains but cannot interconvert fatty acids from one family to another. Although most of the fatty acids consumed in normal nutrition have sixteen (C.sub.16) or eighteen carbon (C.sub.18) chains, the twenty or greater carbon fatty acids, whether ingested or made in the body, are the most important in terms of physiological functions. The .omega.9 fatty acids are primarily elongated to form the twenty carbon eicosatrienoic (C20:3.omega.9) while the most important twenty carbon .omega.6 fatty acid is arachidonic acid (C20:4.omega.6). The .omega.3 fatty acids are normally elongated and desaturated to form either the twenty carbon eicosapentaenoic (C20:5.omega.3) or the twenty-two carbon docosahexaenoic (C22:6.omega.3). The notation (C.sub.-- :.sub.-- .omega..sub.--) indicates the number of carbon atoms in the chain, the number of double bonds, and the class of the fatty acid, respectively.
One of the reasons why the twenty carbon or greater fatty acids are important is their ability to act as substrates in the various prostanoid synthesis pathways, the chemical reactions which form prostaglandins from fatty acids. The first enzyme in this pathway is cyclo-oxygenase which has the .omega.6 fatty acid, arachidonic acid, as its primary substrate in mammals. In the platelets, the arachidonic acid is modified by the enzymes of the pathway to form thromboxane A.sub. 2, a potent platelet aggregator and vasoconstrictor. In the endothelial cells, arachidonic acid is formed into prostacyclin I.sub.2, a vasodilator and platelet antiaggregator. In a number of tissues and organs, including the T-lymphocytes, arachidonic acid is formed into prostaglandin E.sub. 2 which stimulates suppressor T cells and is immunosuppressive. Thromboxane A.sub. 2, prostacyclin I.sub. 2, and prostaglandin E.sub. 2 are all classified as Type "2" prostaglandins.
The same enzyme, cyclo-oxygenase, can also use the .omega.3 fatty acids as substrates. In the platelets, eicosapentaenoic acid is formed into thromboxane A.sub.3 while in the endothelial cells, it is converted into prostacyclin I.sub.3. While prostacyclin I.sub.3 has vasodilatory and platelet antiaggregating properties similar to prostacyclin I.sub. 2, thromboxane A.sub. 3 is only a weak vasoconstrictor and will not aggregate platelets. prostaglandin E.sub. 3, formed in various tissues and organs including the T-lymphocytes, is not immunosuppressive. Thromboxane A.sub. 3, prostacyclin I.sub.3, and prostaglandin E.sub. 3 are Type "3" prostaglandins.
Since both the .omega.3 and .omega.6 fatty acids can be used as substrates for the prostaglandin pathways, it may be possible to modify the prostaglandin mix in the body by modifying the dietary intake ratio of .omega.3 and .omega.6 fatty acids. While there have been some papers showing a change in the ratio of Type 2 to Type 3 by feeding a variety of .omega.3-rich fatty acid materials in place of .omega.6 rich foods, e.g., Sanders et al., Clin. Sci. 61:317-324 (1981), there is not a linear relationship. First, it appears that arachidonic acid is a preferred substrate for cyclo-oxygenase so the .omega.6 fatty acids in the diet are, therefore, used preferentially. Second, absorption of both .omega.3 and .omega.6 long chain fatty acids into the body is slow and may not be equal. Since there seems to be some correlation between an increase in the Type 3 prostaglandins and protection against blood clots and infection, optimal ways of increasing the Type 3/Type 2 prostaglandin ratio are important.
Lowering the .omega.6 fatty acid content and increasing the .omega.3 fatty acid content of the diets should not just improve response to infection, it may lead to an increase in platelet thromboxane A.sub.3 levels. One theory of improving heart patient care is that the "stickiness" of the platelets is affected by the amount of thromboxane A.sub.2, with a higher percentage of thromboxane A.sub.2 leading to "stickier" platelets. By providing more .omega.3 fatty acids to the clo-oxygenase-prostaglandin synthesis pathway, the thromboxane A.sub.3 will be increased at the expense of thromboxane A.sub.2, leading to a lowering of "stickiness" of the platelets and a decrease in the probability of coronary thrombosis. Further, a decrease in thromboxane A.sub. 2 levels has been found to lead to an increase in survival against the challenge of endotoxin. Cook, Wise and Halushka, J. Clin. lnvest. 65:227 (1980).
The absorption of the long chain fatty acids into the body is relatively slow because they required initial hydrolysis and use the lymphatic system. In contrast, MCT's are rapidly absorbed by the body without initial intestinal hydrolysis and through the much faster portal system. It has been reported in "Medium Chain Triglycerides; an update", Bach and Babayan, Am. J. of Cl. Nut. 36:Nov. 1982, pp 951-962, that long chain fatty acids linked to the same glycerol backbone as MCT's will be absorbed faster than conventional triglycerides.
Because of faster absorption, MCT's are useful as a calorie source in the treatment of hospitalized patients. Some hospitalized patients, particularly critically ill patients, require total parenteral nutrition and have a high risk of infection. These patients often have difficulty in obtaining the proper amount of nutrients and energy from the diet; a diet which both minimizes the risk of infection and provides quick nutrition would be of vast benefit to these patients. These diets must provide the essential fatty acids, including a limited amount of specific .omega.6 fatty acids. Most currently available parenteral nutrition systems give much more of the essential fatty acids than is needed because they use soybean or safflower oil as the fatty acid source. These oils contain primarily polyunsaturated .omega.6 fatty acids but have little or no twenty carbon length .omega.3 fatty acid content. Since essential fatty acid nutrition requires that only 2 to 4% of the total calorie intake to be .omega.6 oils and most parenteral nutrition diets supply between 10 and 50% of the calorie intake as oils, there is a large excess of .omega.6 fatty acids being given on these diets.
While calories are important in the diet of a severely stressed patient, the form that calories are supplied in plays a significant role because carbohydrate energy sources, as opposed to fat sources, stimulate insulin release. Insulin release can be harmful in stress states because of problems with insulin resistance. Complications caused by excess carbohydrate content in the diet can include fatty liver, hyperglycemia, and respiratory failure due to excess carbon dioxide production. Usually 30 to 50% of the dietary calories should come from dietary fat to minimize these risks but if long chain fats, particularly having a chain length of sixteen carbons or greater, are used in this quantity, they are cleared very slowly from the circulation and can block the reticuloendothelial system. However, MCT's and structured lipids of MCT and LCT's provide additional fat calories and are rapidly cleared so there is no difficulty with the reticuloendothelial system. Further, and very importantly, the MCT's do not act as substrates for prostaglandin synthesis.
Accordingly, an object of the invention is to provide a method of minimizing the effects of infection and minimizing the effects of subsequent infection in at risk animals, particularly humans, by administering a diet which promotes resistance to infection as well as supplying a readily usable energy source.
Another object of the invention is to provide a dietary supplement which provides sufficient, highly usable nutrition to stressed patients while reducing the risks of infection.
A further object of the invention is to provide a method of treating patients having a high risk of infection with a dietary supplement that provides essential fatty acids while assisting in resistance to infection and heart problems.
A still further object of the invention is to provide a lipid source and a dietary supplement useful in treating stressed patients.
These and other objects and features of the invention will be apparent from the following description.